The effect of changes in membrane lipid composition on the activity of rat liver microsomal acylcoenzyme A:cholesterol acyltransferase (ACAT) activity will be determined. One method for changing microsomal lipid composition will be to feed the rats diets containing different types of fat, including menhaden oil, corn oil and cocoa butter. Another will be to incubate isolated microsomes with different kinds of phospholipids together with phospholipid exchange protein. The cholesterol content of the microsomes also will be modified, either in vivo by diet or in vitro by incubation with liposomes containing different amounts of cholesterol. Attempts will be made to determine the number of different pools of cholesterol in the microsomes and their accessibility to ACAT, using enrichment of the microsomes with radioactive cholesterol. The effects of membrane lipid modifications on other microsomal enzyme activities will be investigated, particularly enzymes involved in lipid metabolism such as NADPH-dependent lipid peroxidation, fatty acid desaturases, acyltransferases involved in phospholipid and triglyceride synthesis and HMGCoA reductase. Finally, the effect of changes in fatty acid saturation on the activity of ACAT in extrahepatic tissues will be examined, including intestinal mucosa, adrenal and one or more types of cultured cells.